View source for 9aym


==Cryo-EM Structure of E.coli produced recombinant N-acetyltransferase 10 (NAT10) in complex with cytidine-acetone-CoA bisubstrate probe==
<StructureSection load='9aym' size='340' side='right'caption='[[9aym]], [[Resolution|resolution]] 3.29&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9aym]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Chaetomium_thermophilum_var._thermophilum_DSM_1495 Chaetomium thermophilum var. thermophilum DSM 1495]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9AYM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9AYM FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.29&#8491;</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=9aym FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9aym OCA], [https://pdbe.org/9aym PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9aym RCSB], [https://www.ebi.ac.uk/pdbsum/9aym PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9aym ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/G0S273_CHATD G0S273_CHATD] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Human NAT10 acetylates the N4 position of cytidine in RNA, predominantly on rRNA and tRNA, to facilitate ribosome biogenesis and protein translation. NAT10 has been proposed as a therapeutic target in cancers as well as aging-associated pathologies such as Hutchinson-Gilford Progeria Syndrome (HGPS). The approximately 120 kDa NAT10 protein uses its acetyl-CoA-dependent acetyltransferase, ATP-dependent helicase, and RNA binding domains in concert to mediate RNA-specific N4-cytidine acetylation. While the biochemical activity of NAT10 is well known, the molecular basis for catalysis of eukaryotic RNA acetylation remains relatively undefined. To provide molecular insights into the RNA-specific acetylation by NAT10, we determined the single particle cryo-EM structures of Chaetomium thermophilum NAT10 ( Ct NAT10) bound to a bisubstrate cytidine-CoA probe with and without ADP. The structures reveal that NAT10 forms a symmetrical heart-shaped dimer with conserved functional domains surrounding the acetyltransferase active sites harboring the cytidine-CoA probe. Structure-based mutagenesis with analysis of mutants in vitro supports the catalytic role of two conserved active site residues (His548 and Tyr549 in Ct NAT10), and two basic patches, both proximal and distal to the active site for RNA-specific acetylation. Yeast complementation analyses and senescence assays in human cells also implicates NAT10 catalytic activity in yeast thermoadaptation and cellular senescence. Comparison of the NAT10 structure to protein lysine and N-terminal acetyltransferase enzymes reveals an unusually open active site suggesting that these enzymes have been evolutionarily tailored for RNA recognition and cytidine-specific acetylation.

Molecular Basis for RNA Cytidine Acetylation by NAT10.,Zhou M, Gamage ST, Tran KA, Bartee D, Wei X, Yin B, Berger S, Meier JL, Marmorstein R bioRxiv [Preprint]. 2024 Mar 27:2024.03.27.587050. doi: , 10.1101/2024.03.27.587050. PMID:38585770<ref>PMID:38585770</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9aym" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Chaetomium thermophilum var. thermophilum DSM 1495]]
[[Category: Large Structures]]
[[Category: Marmorstein R]]
[[Category: Zhou M]]